Progression Of Endometriosis Research Articles

Role of the gut microbiota in the pathogenesis of endometriosis: a review.

Endometriosis is classically defined as a chronic inflammatory heterogeneous disorder occurring in any part of the body, characterized by estrogen-driven periodic bleeding, proliferation, and fibrosis of ectopic endometrial glands and stroma outside the uterus. Endometriosis can take overwhelmingly serious damage to the structure and function of multi-organ, even impair whole-body systems, resulting in severe dysmenorrhea, chronic pelvic pain, infertility, fatigue and depression in 5-10% women of reproductive age. Precisely because of a huge deficiency of cognition about underlying etiology and complex pathogenesis of the debilitating disease, early diagnosis and treatment modalities with relatively minor side effects become bottlenecks in endometriosis. Thus, endometriosis warrants deeper exploration and expanded investigation in pathogenesis. The gut microbiota plays a significant role in chronic diseases in humans by acting as an important participant and regulator in the metabolism and immunity of the body. Increasingly, studies have shown that the gut microbiota is closely related to inflammation, estrogen metabolism, and immunity resulting in the development and progression of endometriosis. In this review, we discuss the diverse mechanisms of endometriosis closely related to the gut microbiota in order to provide new approaches for deeper exploration and expanded investigation for endometriosis on prevention, early diagnosis and treatment.

An Examination of the Association Between Types of Menopausal Hormone Therapy (Estrogen-Only Hormone Therapy Versus Combined-Hormone-Therapy Versus Tibolone) and Endometriosis Progression in Peri/Postmenopausal Women With a Previous Hysterectomy

An Examination of the Association Between Types of Menopausal Hormone Therapy (Estrogen-Only Hormone Therapy Versus Combined-Hormone-Therapy Versus Tibolone) and Endometriosis Progression in Peri/Postmenopausal Women With a Previous Hysterectomy

18F-FDG PET/CT findings of endometriosis and corpus luteum cyst.

SynopsisPET/CT can differentiate between endometriosis, the malignant progression of endometriosis, and ovarian cysts.

The Association Between Daily Intake of Dietary Supplements and Self-Reported Endometriosis: A NHANES-Based Study.

Dietary supplements are gaining recognition as potential influencers of female reproductive health, but their connection to endometriosis risk remains underexplored. This study addressed this gap, examining the impact of daily dietary supplement intake on the initiation and progression of endometriosis. To explore this, a cross-sectional study was conducted involving 3950 participants representative of the US population from the 1999-2006 National Health and Nutrition Examination Survey (NHANES). Infertility was determined by a question on year-long attempts to become pregnant. Unweighted and weighted multivariate logistic regression analyses assessed the association between dietary supplements and endometriosis risk. Subgroup analysis was conducted based on the participants' body mass index (BMI). The results revealed intriguing patterns. Specifically, higher dietary fiber content (Q4 vs Q1: OR = 0.56, 95% CI = (0.37,0.84), P = 0.0062) and density (Q4 vs Q1: OR = 0.55, 95% CI = (0.38,0.81), P = 0.0035) were linked to reduced risk of endometriosis. Protein content (Q4 vs Q1: OR = 0.47, 95% CI = (0.31,0.74), P = 0.0011) and density (Q4 vs Q1: OR = 0.63, 95% CI = (0.45,0.88), P = 0.0096) similarly exhibited a negative association with endometriosis risk. Interestingly, when stratified by BMI, these effects were pronounced in normal-weight women, whereas they were not evident in the overweight and obese subgroup. Protein content and density showed no significant associations across subpopulations. In conclusion, this study established a negative relationship between dietary fiber and endometriosis, particularly notable in normal-weight women. Future research is essential to validate these findings and establish a causal link between dietary fiber and endometriosis.

Role of Cyclins and Cytoskeletal Proteins in Endometriosis: Insights into Pathophysiology.

Endometriosis is a gynecological condition where endometrium-like tissue grows outside the uterus, posing challenges in understanding and treatment. This article delves into the deep cellular and molecular processes underlying endometriosis, with a focus on the crucial roles played by cyclins and cytoskeletal proteins in its pathogenesis, particularly in the context of Epithelial-Mesenchymal Transition (EMT). The investigation begins by examining the activities of cyclins, elucidating their diverse biological roles such as cell cycle control, proliferation, evasion of apoptosis, and angiogenesis among ectopic endometrial cells. A comprehensive analysis of cytoskeletal proteins follows, emphasizing their fundamental biological roles and their specific significance to endometriotic cell features. This review sheds light on the interconnected pathways through which cyclins and cytoskeletal proteins converge, contributing to the genesis and progression of endometriosis. Understanding these molecular complexities not only provides insight into the underlying causes of the disease but also holds promise for the development of specific therapeutic approaches, ushering in a new era in the management of this devastating disorder.

Transcription factor EB-mediated autophagy affects cell migration and inhibits apoptosis to promote endometriosis.

Autophagy has emerged as an important process of cell metabolism. With continuous in-depth research on autophagy, TFEB has been a key transcription factor regulating autophagy levels in recent years. Studies have established that TFEB regulates autophagy and apoptosis in various diseases. However, the relationship between TFEB and the pathogenesis of endometriosis remains unclear. This study aimed to investigate the effect of TFEB on the mechanism of endometriosis progression. The results showed that TFEB and autophagy-related protein LC3 are highly expressed in ectopic endometrium of patients with endometriosis, overexpression of TFEB in cultured human endometrial stromal cells (HESCs) by lentivirus not only promoted autophagy but also inhibited apoptosis. In addition, the migration and invasion ability of HESCs were enhanced by TFEB overexpression. Furthermore, inhibiting autophagy with specific inhibitors can attenuate migration and invasion of HESCs induced by TFEB. The rat models of endometriosis show that TFEB knockdown can suppress lesion growth in vivo. Our results suggest that autophagy may be involved in the progression mechanism of endometriosis, and the mechanism of autophagy disorder in endometriosis is probably related to TFEB. TFEB may be a key molecule in promoting endometriosis.

Transcriptomic changes in eutopic endometrium and ectopic lesions during endometriosis progression in a mouse model

ObjectiveTo identify the transcriptomic changes of ectopic lesions and eutopic endometrial tissues during the progression of endometriosis. HypothesisOur hypothesis is that development and progression of endometriosis change transcriptome in the eutopic endometrium and ectopic lesions DesignLaboratory study. SettingAcademic Medical Center AnimalsFour fertile and four subfertile Pgrcre/+Rosa26mTmG/+ mice with endometriosis, and four sham mice for each group of endometriosis mice as control. These mice underwent either surgery to induce endometriosis or sham surgery. Fertile sham and mice with endometriosis were used one month after surgery, while subfertile ones were used three months after surgery. InterventionsEarly and chronic effect of endometriosis on transcriptomics of ectopic lesions and eutopic endometrium Main Outcome MeasuresRNA-Sequencing analysis (RNA-Seq) and identification of differential expressed genes and pathways in the ectopic lesions and eutopic uteri from mice with endometriosis and sham mice at day of pregnancy 3.5. ResultsOur mouse model recapitulates the transcriptomic changes of ectopic lesions in human. RNA-seq was performed in ectopic lesions and eutopic uteri from mice with or without endometriosis during progression of disease. Estradiol, inflammation, angiogenesis, and fibrosis pathways were consistently elevated in all the ectopic lesions compared to eutopic endometrium. Cholesterol/glucose synthesis and stem cell pluripotency pathways were more enhanced in ectopic lesions from subfertile mice compared to their eutopic endometrium. Dysregulation of infiltration of macrophage, dendritic, T and B cells were validated by using immunohistochemistry in ectopic lesions. multiple ligand-receptor pairs between the ectopic and eutopic endometrium were altered compared to the sham endometrium. Suppressed WNT and EGF pathways were only found in the eutopic endometrium from subfertile not fertile mice compared to sham. ConclusionsOur mouse endometriosis model recapitulates the transcriptomics of ectopic lesions in humans. Our transcriptomic analysis during endometriosis progression in our mouse model will help understand the pathophysiology of endometriosis.

Role of TGF-Beta in the progression and development of endometriosis

Role of TGF-Beta in the progression and development of endometriosis

Extracellular succinate derived from ectopic milieu drives adhesion and implantation growth of ectopic endometrial stromal cells via the SUCNR1 signal in endometriosis

BackgroundAs a dual-function metabolite, succinate has emerged in cell function and plays a key signaling role in linking mitochondrial function to other cellular functions. Succinate accumulation in the cytoplasm is commonly associated with hypoxia in the microenvironment and immune cell activation. Extracellular succinate released into the microenvironment is considered an inflammatory alarm that can be sensed by its membrane receptor SUCNR1, which boosts proinflammatory responses and acts akin to classical hormones and cytokines. Succinate plays an important role in the development of inflammatory diseases. Whether succinate facilitates the progression of endometriosis (EMs), characterized by chronic inflammation and peritoneal adhesion, is worth exploring.ObjectiveWe mimicked the ectopic milieu in vitro and in vivo to evaluate the main source and potential role of succinate in endometriosis. We assessed the molecular and functional effects of succinate on macrophages and peritoneal mesothelial cells in peritoneal cavity. The effect of succinate/SUCNR1 signaling on ectopic endometrial stromal cells (ESCs) was further explored in this study.MethodsIn this study, we used targeted organic acid metabolomics analysis and in vitro assays to assess the potential accumulation of succinate in the peritoneal fluid of EMs patients. We examined its correlation with disease severity, Visual Analogue Scale, and the Endometriosis Fertility Index. Flow cytometry, enzyme linked immunosorbent assay, western blot assay, quantitative real-time PCR, and other molecular biology techniques were used to explore the potential mechanisms.ResultsBy mimicking the ectopic milieu, we constructed an in vitro co-culture system and found that M1 polarized macrophages and that the peritoneal mesothelial cell line (HMrSV5) mainly released succinate into their microenvironment and activated the succinate receptor (SUCNR1) signal, which further polarized the macrophages and significantly enhanced the invasive survival of ESCs, and the adhesion to the peritoneum. We further investigated the pathological effects of extracellular succinate in vivo using a xenograft mouse models of endometriosis.ConclusionsSuccinate-SUCNR1 signaling facilitates the creation of inflammatory cells and plays a vital role in EMs progression and peritoneal adhesion. Our work on the molecular mechanisms underlying succinate accumulation and function will help elucidate the phenotypic mysteries of pain and infertility in EMs.BkiB34NQBDvkGHWZYD1GB2Video

Patterns of proliferation and fibrosis in a rat model of endometriosis following administration of Allium cepa.

Endometriosis is a common gynecological disease among reproductive-age women. Numerous hypotheses exist regarding the pathogenesis of endometriosis. In Turkey, the consumption of Allium cepa (commonly known as the "onion cure") is a popular treatment employed to alleviate a variety of gynecological disorders. In this study, our objective was to assess the therapeutic mechanisms of the onion bulb A. cepa using an autologous endometriosis model in Sprague-Dawley rats. Previous research has shown that A. cepa possesses anti-inflammatory, antioxidant, and antiapoptotic properties. We evaluated the pathological condition of endometriotic implants by employing hematoxylin-eosin staining and Ki67 immunohistochemistry analysis. Transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) have been identified as profibrotic markers that are highly overexpressed in endometriotic tissues relative to eutopic endometrial tissue. Furthermore, TGF-β1 influences the differentiation and progression of endometriosis. To quantify profibrotic activity, we measured TGF-β1 and α-SMA using the immunosorbent assay method. Lower histologic evaluation scores for endometriotic implants were observed in the group receiving high-dose A. cepa relative to the other groups. Ki67 expression was reduced following the high-dose A. cepa regimen, which consisted of 30% A. cepa and 70% normal feed. However, no statistically significant differences in TGF-β1 or α-SMA levels were observed among the groups (p=0.7 and p=0.778, respectively). The findings suggest that A. cepa could serve as a therapeutic agent in endometriosis treatment, as evidenced by the reduction in proliferative potential. Nevertheless, A. cepa was not associated with significantly lower levels of endometriosis-associated TGF-β1 or α-SMA.

ERβ-activated LINC01018 promotes endometriosis development by regulating the CDC25C/CDK1/CyclinB1 pathway

Endometriosis refers to as an estrogen-dependent disease. Estrogen receptor β (ERβ), the main estrogen receptor subtype which is encoded by the estrogen receptor 2 (ESR2) gene, can mediate the action of estrogen in endometriosis. Although selective estrogen receptor modulators can target the ERβ, they are not specific due to the wide distribution of ERβ. Recently, long noncoding RNAs have been implicated in endometriosis. Therefore, we aim to explore and validate the downstream regulatory mechanism of ERβ, and to investigate the potential role of long intergenic noncoding RNA 1018 (LINC01018) as a nonhormonal treatment for endometriosis. Our study demonstrates that the expression levels of ESR2 and LINC01018 are increased in ectopic endometrial tissues and reveals a significant positive correlation between the ESR2 and LINC01018 expression. Mechanistically, ERβ directly binds to an estrogen response element located in the LINC01018 promoter region and activates LINC01018 transcription. Functionally, ERβ can regulate the CDC25C/CDK1/CyclinB1 pathway and promote ectopic endometrial stromal cell proliferation via LINC01018 in vitro. Consistent with these findings, the knockdown of LINC01018 inhibits endometriotic lesion proliferation in vivo. In summary, our study demonstrates that the ERβ/LINC01018/CDC25C/CDK1/CyclinB1 signaling axis regulates endometriosis progression.

Implication of biosignatures in the progression of endometriosis

Endometriosis is an estrogen-dependent chronic inflammatory disorder involving the placement and growth of endometrial tissue outside the uterine cavity. It is the most common multifactorial disease that affects the life quality of women in reproductive age. Due to its multicomponent nature, early diagnosis of the disease is challenging. Since many genetic, epigenetic alterations and non-genetic factors contribute to the pathology of endometriosis, devising a drug therapy that directly acts on the ectopic tissue is extremely difficult. Endometriosis is a hormone-driven disease with estrogen considered as a primary driver for the development of endometriotic lesions. This study aims to identify biosignatures involved in endometriosis with and without gonadotropin releasing hormone agonists (GnRHa). GnRHa is a short peptide analog of GnRH that causes inhibition of estrogen and androgen synthesis. Microarray based-gene expression profiling was performed on total RNA extracted from endometriotic tissue samples with and without GnRHa-treated patients already published in our previous paper. The untreated group were considered as the control. Genes were then selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). qRT-PCR analysis confirmed significant downregulation in(p < 0.05) expression of DARC (p = 0.0042), CDH1 (p = 0.0027), CDH5 (p = 0.0283), ATP2A3 (p < 0.001), RGS5 (p = 0.0032), and CD36 (p = 0.0162) in endometriosis patients treated with GnRHa analogs. Although, CTNNAL1 (p = 0.0136) also showed significant results but there was upregulation in their expression levels after GnRHa treatment. Thus, an altered expression of these genes makes them a possible candidate determinant of endometriosis treated with GnRHa.

How Can Selected Dietary Ingredients Influence the Development and Progression of Endometriosis?

Endometriosis is a chronic, hormone-dependent disease characterized by the presence of endometrial tissue in ectopic locations. Since the treatment options for this disease are still limited, and the cure rate is unsatisfactory, the search for ways to treat symptoms and modify the course of the disease is of key importance in improving the quality of life of patients with endometriosis. So far, the literature has shown that nutrition can influence endometriosis through hormonal modification and altering the inflammatory or oxidative response. Since the importance of nutrition in this disease is still a subject of scientific research, we aimed to summarize the current knowledge on the role of dietary modifications in endometriosis. Our review showed that nutrients with anti-inflammatory and antioxidant properties, including most vitamins and several trace elements, may influence the pathogenesis of endometriosis and can be considered as the nutrients preventing the development of endometriosis. However, despite the many discoveries described in this review, further interdisciplinary research on this topic seems to be extremely important, as in the future, it may result in the development of personalized therapies supporting the treatment of endometriosis.

Molecular mechanism of autophagy and apoptosis in endometriosis: Current understanding and future research directions.

Endometriosis is a common gynecological condition, with symptoms including pain and infertility. Regurgitated endometrial cells into the peritoneal cavity encounter hypoxia and nutrient starvation. Endometriotic cells have evolved various adaptive mechanisms to survive in this inevitable condition. These adaptations include escape from apoptosis. Autophagy, a self-degradation system, controls apoptosis during stress conditions. However, to date, the mechanisms regulating the interplay between autophagy and apoptosis are still poorly understood. In this review, we summarize the current understanding of the molecular characteristics of autophagy in endometriosis and discuss future therapeutic challenges. A search of PubMed and Google Scholar databases were used to identify relevant studies for this narrative literature review. Autophagy may be dynamically regulated through various intrinsic (e.g., PI3K/AKT/mTOR signal transduction network) and extrinsic (e.g., hypoxia and iron-mediated oxidative stress) pathways, contributing to the development and progression of endometriosis. Upregulation of mTOR expression suppresses apoptosis via inhibiting the autophagy pathway, whereas hypoxia or excess iron often inhibits apoptosis via promoting autophagy. Endometriotic cells may have acquired antiapoptotic mechanisms through unique intrinsic and extrinsic autophagy pathways to survive in changing environments.

Role of Pyroptosis in Endometrial Cancer and Its Therapeutic Regulation.

Pyroptosis is an inflammatory cell death induced by inflammasomes that release several pro-inflammatory mediators such as interleukin-18 (IL-18) and interleukin-1β (IL-1β). Pyroptosis, a type of programmed cell death, has recently received increased interest both as a therapeutic and immunological mechanism. Numerous studies have provided substantial evidence supporting the involvement of inflammasomes and pyroptosis in a variety of pathological conditions including cancers, nerve damage, inflammatory diseases and metabolic conditions. Researchers have demonstrated that dysregulation of pyroptosis and inflammasomes contribute to the progression of endometriosis and gynecological malignancies. Current research also indicates that inflammasome and pyroptosis-dependent signaling pathways may further induce the progression of endometrial cancer (EC). More specifically, dysregulation of NLR family pyrin domain 3 (NLRP3) and caspase-1-dependent pyroptosis play a contributory role in the pathogenesis and development of EC. Therefore, pyroptosis-regulated protein gasdermin D (GSDMD) may be an independent prognostic biomarker for the detection of EC. This review presents the molecular mechanisms of pyroptosis-dependent signaling pathways and their contributory role and function in advancing EC. Moreover, this review offers new insights into potential future applications and innovative approaches in utilizing pyroptosis to develop effective anti-cancer therapies.

Isolation of myeloid-derived suppressor cells (MDSC) from endometriotic mice model and their immunomodulatory functions.

Endometriosis is a chronic, painful disease whose etiology remains unknown. The development of novel therapies and diagnostic tools for endometriosis has been limited due in part to challenges in studying the disease. Recently, a few reports have shown that immunosuppressive cells, such as myeloid-derived suppressor cell (MDSC), may promote the progression of endometriosis. MDSCs are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here, in this chapter, we provide a detailed protocol to phenotype MDSC as well as to isolate and assess the functionality from the peritoneal cavity of a mouse model of surgically induced endometriosis. Importantly, the current mouse model has been widely used to study how the immune system, hormones, and environmental factors affect endometriosis as well as the effects of endometriosis on fertility and pain.

Hypomethylation of the ENPP3 promoter region contributes to the occurrence and development of ovarian endometriosis via the AKT/mTOR/4EBP1 signaling pathway.

Growing evidence indicates that aberrant methylation is pivotal in the development and progression of endometriosis (EMs). This study explores the relationship between abnormal methylation of the ENPP3 promoter and the pathogenesis of ovarian EMs, focusing on its regulatory effect on ENPP3 expression. We analyzed the methylation levels of ENPP3 in ectopic endometrial tissues from ovarian EMs patients and in normal endometrial tissues from women without EMs. The expression and distribution of ENPP3 were evaluated using RT-qPCR and immunohistochemistry. Transwell assays were conducted to examine the impact of ENPP3 overexpression on the migratory and invasive capabilities of endometrial stromal cells. Our results demonstrated significantly reduced methylation levels at the CpG sites of the ENPP3 promoter region in ectopic endometrial tissues compared to normal endometrial tissues. RT-qPCR findings revealed a marked increase in ENPP3 expression in ovarian EMs tissues relative to endometrial tissues from patients without EMs, and this upregulation was negatively correlated with the methylation levels of the ENPP3 promoter region. Immunohistochemical analyses confirmed elevated ENPP3 expression in the glandular epithelial cells and stroma of ovarian EMs tissues. Furthermore, in vitro experiments showed that overexpressed ENPP3 notably intensified the invasion and migration of endometrial stromal cells. Transcriptome sequencing and functional analyses indicated that the increased ENPP3 expression activated the AKT/mTOR/4EBP1 signaling pathway. In summary, the study suggests that hypomethylation in the ENPP3 promoter region may contribute to the initiation and advancement of ovarian EMs by activating the AKT/mTOR/4EBP1 pathway, supporting the theory that EMs might be an epigenetically regulated disorder.

Sonomorphologic Changes in Colorectal Deep Endometriosis: The Long-Term Impact of Age and Hormonal Treatment.

The progression of deep endometriosis (DE) in women of reproductive age is highly variable. This study aimed to analyze the sonomorphological changes of rectal endometriosis over long periods of time and the influence of hormonal treatment. This retrospective study included premenopausal women with rectal DE treated conservatively between 2002 and 2021. The lesion length and thickness of the nodule were evaluated at regular intervals over time. We created statistical models with mixed effects to identify potential factors influencing lesion progression and regression. 38 patients were monitored over a mean period of 7.2 (± 4.2) years with a mean of 3.1 (± 2.1) check-ups within the observation period. We detected a significant increase in lesion length until the end of the fourth decade of life. In addition, we found a substantial decrease in the length and thickness of the nodule depending on the length of hormonal treatment. In conservatively managed patients with rectal endometriosis, without hormonal therapy, lesion size can exhibit a moderate increase up to the end of the fourth decade of life, after which it appears to stabilize. This increase does not follow a linear pattern. Hormonal therapy is crucial in impeding further progression, resulting in either a cessation or a regression of lesion growth.

The PES1/FOXM1 heterodimer suppresses TCF21 and ERβ expression in ovarian endometriosis

AbstractTranscription factor 21 (TCF21) and estrogen receptor beta (ERβ, encoded by ESR2) are highly expressed in endometriotic stromal cells (ESCs) and contribute to the pathogenesis of endometriosis. However, the exploration of TCF21 and ERβ expression regulation at the molecular level remains limited. Here, by using bioinformatics analysis and experimental verification, we identified PES1, also known as Pescadillo, as a negative regulator in the development of endometriosis that downregulates TCF21 and ERβ expression in ESCs. PES1 overexpression regulated critical biological processes involved in endometriosis development, such as invasion and apoptosis. A coimmunoprecipitation assay showed that PES1 could form a complex with Forkhead box M1 (FOXM1). Further analyses elucidated that siPES1 in ectopic lesions decreased the stability of FOXM1 protein and reduced the binding activities of FOXM1 to TCF21 and ESR2 promoters, thus weakening the transcriptional inhibition of TCF21 and ERβ by FOXM1. Moreover, in an endometriosis mouse model, overexpressing PES1 effectively reduced the growth of ectopic lesions and suppressed TCF21 and ERβ expression, which suggests a promising therapeutic strategy for endometriosis. Collectively, our results indicate that the loss of PES1 in ectopic lesions contributes to endometriosis progression by upregulating ERβ and TCF21 expression through heterodimer formation with FOXM1. Moreover, targeting PES1 could serve as a treatment method for endometriosis.

Machine learning algorithms for a novel cuproptosis-related gene signature of diagnostic and immune infiltration in endometriosis

Endometriosis (EMT) is an aggressive disease of the reproductive system, also called “benign cancer”. However, effective treatments for EMT are still lacking in clinical practice. Interestingly, immune infiltration is significantly involved in EMT pathogenesis. Currently, no studies have shown the involvement of cuproptosis-related genes (CRGs) in regulating immune infiltration in EMT. This study identified three CRGs such as GLS, NFE2L2, and PDHA1, associated with EMT using machine learning algorithms. These three CRGs were upregulated in the endometrium of patients with moderate/severe EMT and downregulated in patients with infertility. Single sample genomic enrichment analysis (ssGSEA) revealed that these CRGs were closely correlated with autoimmune diseases such as systemic lupus erythematosus. Furthermore, these CRGs were correlated with immune cells such as eosinophils, natural killer cells, and macrophages. Therefore, profiling patients based on these genes aid in a more accurate diagnosis of EMT progression. The mRNA and protein expression levels of GLS, NFE2L2 and PDHA1 were validated by qRT-PCR and WB studies in EMT samples. These findings provide a new idea for the pathology and treatment of endometriosis, suggesting that CRGs such as GLS, NFE2L2 and PDHA1 may play a key role in the occurrence and development of endometriosis.